The incorporation of fullerenes into macromolecular structures of biological importance has been a continual pursuit of researchers over the course of the past decade. “Buckminsterfullerene,” C60, or [60] fullerene (names which all refer to the same molecule), is well known for its unique hydrophobic nature and other physiochemical properties that make it an interesting pharmocophore candidate. For instance, C60 and other fullerenes can be incorporated into the cylindrical hydrophobic cavity (or cavities) of HIV protease and behave as an inhibitor. See Friedman et al., J. Am. Chem. Soc., 1993, 115, pp. 6506-6509. In vitro studies of water soluble-[60] fullerene derivatives containing hydrophilic functionalities show that they can inhibit acutely- and chronically-affected peripheral blood mononuclear cells with an EC50 (50% effective concentration) as low as 7 μM. See Sijbesma et al., J. Am. Chem. Soc., 1993, 115, pp. 6510-6512. Active oxygen species can be generated from photoexcited fullerenes as potential medicines. See Yamakoshi et al., J. Am. Chem. Soc., 2003, 125, pp. 12803-12809. This makes fullerenes and their derivatives excellent candidates for use in photodynamic therapy (PDT) for cancer treatment. Therefore, building bioactive [60] fullerene derivatives is not merely of scholarly interest, but also of considerable medicinal significance.
Amino acids are a basic and essential building block for living organisms at all levels. Indeed, they polymerize into polypeptides or proteins, proteins being responsible for much of the mechanistic phenomenon within biological organisms (e.g. enzymes, antibodies, ion channels, hemoglobin, etc.). The idea of combining fullerenes with amino acid residues has long been of great interest to chemists. The incorporation of fullerene-based amino acids into proteins, peptides or antibodies could lead to many new applications in the realm of medicinal chemistry. Possible interactions of fullerene with hydrophobic pocket(s), or other arene-arene interactions, within proteins or enzymes could provide new insight into the function-structure study of such proteins and enzymes. However, to build molecules with [60] fullerene as an inseparable part of the amino acid, i.e., an amino acid resembling a natural one and having the general formula:
and denoted hereafter as H2N—CH(R)—C(O)—OH, and which can survive through the entire biological range of pH changes and enzymatic cleavage and stay whole, remains a challenge. So far, reports of fullerene-based amino acids are still rare, and these generally contain an amide or ester link. Such linkages are susceptible to cleavage by hydrolysis. Considerable effort in fullerene chemistry has shown that this task is not trivial, since C60 itself readily reacts with nucleophiles and also reacts under many hydrogenation conditions. The latter scenario represents a major obstacle for its use in many chemical processes. Methods and compositions that serve to overcome some of these obstacles would be very beneficial.